Insertion site monitoring methods and related infusion devices and systems

ABSTRACT

Infusion systems, infusion devices, and related operating methods are provided. An exemplary method of operating an infusion device involves obtaining one or more measurement values of a physiological condition in the body of a user during an initial monitoring period and determining a fasting reference value for a metric based on the one or more measurement values. After the initial monitoring period, the method continues by obtaining an updated measurement value during a fasting period, determining a current value for the metric based at least in part on the updated measurement value, and generating a notification in response to a deviation between the current value and the fasting reference value exceeding a threshold indicative of insertion site loss or other loss of effectiveness.

TECHNICAL FIELD

Embodiments of the subject matter described herein relate generally tomedical devices, and more particularly, embodiments of the subjectmatter relate to detecting insertion site conditions during operation ofa fluid infusion device.

BACKGROUND

Infusion pump devices and systems are relatively well known in themedical arts, for use in delivering or dispensing an agent, such asinsulin or another prescribed medication, to a patient. A typicalinfusion pump includes a pump drive system which typically includes asmall motor and drive train components that convert rotational motormotion to a translational displacement of a plunger (or stopper) in areservoir that delivers medication from the reservoir to the body of auser via a fluid path created between the reservoir and the body of auser. Use of infusion pump therapy has been increasing, especially fordelivering insulin for diabetics. Continuous insulin infusion providesgreater control of a patient with diabetes glucose levels, and hence,control schemes are being developed that allow insulin infusion pumps tomonitor and regulate a user's blood glucose level in a substantiallycontinuous and autonomous manner.

In practice, it is advisable for the infusion set being utilized withthe infusion device to be changed or replaced periodically to preventinfection. To mitigate tissue resistance and maintain effectiveness ofinsulin absorption, it is also advisable to periodically change or varythe location where the infusion set is inserted into the body, alsoknown as the insertion site. Failure to timely change the infusion setor the insertion site can have undesirable physiological consequences,such as a potential hyperglycemic event. Accordingly, patients havetypically been instructed to replace infusion sets within a fixed periodof time (e.g., every 2 to 3 days) that attempts to ensure preemptivereplacement that provides a safety margin in advance of the time of whena particular infusion set at a particular insertion site is likely tolose effectiveness. Preemptively replacing an infusion set can bebeneficial for safety purposes, but it may also result in some infusionsets being replaced prematurely when it could otherwise be desirable tomaximize the lifetime of the infusion set. For example, patients who aretraveling, have a limited supply of infusion sets on hand, do not haveimmediate access to an infusion set, or experiencing other extenuatingcircumstances may prefer to avoid having to replace an infusion setaccording to a fixed schedule.

Additionally, some patients may forget to replace or rotate theirinfusion set. While providing reminders based on a fixed period of timemay be effective, some patients may disregard or ignore the messagesbased on a perception that the infusion set is still functioningnormally. Accordingly, there is a need to prolong the usable lifetime ofan infusion set while also ensuring that patients are notified in atimely manner before any adverse events.

BRIEF SUMMARY

Infusion systems, infusion devices, and related operating methods areprovided. An embodiment of a method of operating an infusion device todeliver fluid capable of influencing a physiological condition to a bodyof a user is provided. The method involves obtaining, from a sensingarrangement providing sensed measurements of the physiological conditionin the body of the user, one or more measurement values during aninitial monitoring period and determining a fasting reference value fora metric based on the one or more measurement values. After the initialmonitoring period, the method continues by obtaining, from the sensingarrangement, an updated measurement value during a fasting period,determining a current value for the metric based at least in part on theupdated measurement value, and generating a notification in response toa deviation between the current value and the fasting reference valueexceeding a threshold.

Another embodiment of operating an infusion device operable to deliverinsulin to a body of a patient involves obtaining, from a sensingarrangement, sensed glucose measurement values of a glucose level in thebody of the patient during fasting periods during an initial periodafter initialization of an infusion set associated with the infusiondevice, determining a fasting amount of insulin in the body of thepatient during the fasting periods, and determining a reference insulinestimate for achieving a reference glucose value based at least in parton the fasting amount of insulin and the sensed glucose measurementvalues. After the initial period, the method continues by obtaining,from the sensing arrangement, an updated glucose measurement valueduring a subsequent fasting period, determining a current amount ofinsulin in the body of the patient, determining a current insulinestimate for achieving the reference glucose value based at least inpart on the current amount of insulin and the updated glucosemeasurement value, and generating an insertion site notification basedon a relationship between the current insulin estimate and the referenceinsulin estimate.

In another embodiment, an apparatus of an infusion device is provided.The infusion device includes a communications interface to receivesensed measurements of a physiological condition in a body of a user, afluid interface providing fluid communication with an infusion set todeliver fluid influencing the physiological condition to the body of theuser, a user interface, and a control module coupled to thecommunications interface and the user interface. The control module isconfigurable to obtain one or more fasting measurement values for thephysiological condition from the sensed measurements corresponding tofasting periods during an initial period of a lifetime of the infusionset, determine a fasting reference value for a metric based on the oneor more fasting measurement values, and after the initial period, obtainan updated measurement value from the sensed measurements correspondingto a subsequent fasting period, determine a current value for the metricbased at least in part on the updated measurement value, and provide anotification via the user interface based on a difference between thecurrent value and the fasting reference value.

This summary is provided to introduce a selection of concepts in asimplified form that are further described below in the detaileddescription. This summary is not intended to identify key features oressential features of the claimed subject matter, nor is it intended tobe used as an aid in determining the scope of the claimed subjectmatter.

BRIEF DESCRIPTION OF THE DRAWINGS

A more complete understanding of the subject matter may be derived byreferring to the detailed description and claims when considered inconjunction with the following figures, wherein like reference numbersrefer to similar elements throughout the figures, which may beillustrated for simplicity and clarity and are not necessarily drawn toscale.

FIG. 1 depicts an exemplary embodiment of an infusion system;

FIG. 2 depicts a plan view of an exemplary embodiment of a fluidinfusion device suitable for use in the infusion system of FIG. 1;

FIG. 3 is an exploded perspective view of the fluid infusion device ofFIG. 2;

FIG. 4 is a cross-sectional view of the fluid infusion device of FIGS.2-3 as viewed along line 4-4 in FIG. 3 when assembled with a reservoirinserted in the infusion device;

FIG. 5 is a block diagram of an exemplary control system suitable foruse in a fluid infusion device, such as the fluid infusion device ofFIG. 1 or FIG. 2;

FIG. 6 is a block diagram of an exemplary pump control system suitablefor use in the control system of FIG. 5;

FIG. 7 is a block diagram of a closed-loop control system that may beimplemented or otherwise supported by the pump control system in thefluid infusion device of FIG. 5 in one or more exemplary embodiments;

FIG. 8 is a flow diagram of an exemplary site monitoring processsuitable for use with the control system of FIG. 5 in one or moreexemplary embodiments; and

FIG. 9 is a flow diagram of an exemplary site loss detection processsuitable for use with the control system of FIG. 5 in conjunction withthe site monitoring process of FIG. 8 in one or more exemplaryembodiments.

DETAILED DESCRIPTION

The following detailed description is merely illustrative in nature andis not intended to limit the embodiments of the subject matter or theapplication and uses of such embodiments. As used herein, the word“exemplary” means “serving as an example, instance, or illustration.”Any implementation described herein as exemplary is not necessarily tobe construed as preferred or advantageous over other implementations.Furthermore, there is no intention to be bound by any expressed orimplied theory presented in the preceding technical field, background,brief summary or the following detailed description.

While the subject matter described herein can be implemented in anyelectronic device, exemplary embodiments described below are implementedin the form of medical devices, such as portable electronic medicaldevices. Although many different applications are possible, thefollowing description focuses on a fluid infusion device (or infusionpump) as part of an infusion system deployment. For the sake of brevity,conventional techniques related to infusion system operation, insulinpump and/or infusion set operation, and other functional aspects of thesystems (and the individual operating components of the systems) may notbe described in detail here. Examples of infusion pumps may be of thetype described in, but not limited to, U.S. Pat. Nos. 4,562,751;4,685,903; 5,080,653; 5,505,709; 5,097,122; 6,485,465; 6,554,798;6,558,320; 6,558,351; 6,641,533; 6,659,980; 6,752,787; 6,817,990;6,932,584; and 7,621,893; each of which are herein incorporated byreference.

Embodiments of the subject matter described herein generally relate toinfusion systems including a fluid infusion device having a motor orother actuation arrangement that is operable to linearly displace aplunger (or stopper) of a reservoir provided within the fluid infusiondevice to deliver a dosage of fluid, such as insulin, to the body of apatient (or user). Dosage commands that govern operation of the motormay be generated in an automated manner in accordance with the deliverycontrol scheme associated with a particular operating mode, and thedosage commands may be generated in a manner that is influenced by acurrent (or most recent) measurement of a physiological condition in thebody of the user. For example, in a closed-loop operating mode, dosagecommands may be generated based on a difference between a current (ormost recent) measurement of the interstitial fluid glucose level in thebody of the user and a target (or reference) glucose value. In thisregard, the rate of infusion may vary as the difference between acurrent measurement value and the target measurement value fluctuates.For purposes of explanation, the subject matter is described herein inthe context of the infused fluid being insulin for regulating a glucoselevel of a user (or patient); however, it should be appreciated thatmany other fluids may be administered through infusion, and the subjectmatter described herein is not necessarily limited to use with insulin.

As described in greater detail below, primarily in the context of FIGS.8-9, in exemplary embodiments described herein, the infusion devicemonitors sensed glucose measurement values for changes in a patient'sfasting glucose levels over the lifetime of an infusion set andgenerates an alert or notification when the magnitude of the change infasting glucose levels indicates that the infusion set should bereplaced, inspected, rotated, or otherwise attended to. In this regard,as the effectiveness of the current infusion set or the currentinsertion site wanes (e.g., due to increasing tissue resistance ordecreased absorption), fasting glucose values trend upward incorrelation with the lifetime of the infusion set. Accordingly, changesin the patient's fasting glucose levels can be utilized to detectinsertion site loss or other potential problems associated with theinfusion set or insertion site. By providing a timely notification tochange an infusion set when a patient's daily glucose profile or fastingglucose levels drifts towards higher glucose values, potentialhyperglycemic events can be avoided. At the same time, by virtue of themonitoring of fasting glucose levels, infusion sets do not need to bepreemptively replaced, which, in turn may allow for the usable life ofthe infusion set to be increased beyond a fixed replacement schedule.

In exemplary embodiments, during an initial monitoring period after aninfusion set is initialized or changed, the infusion device obtainssensed glucose measurement values that are coincident with,contemporaneous to, or otherwise temporally correspond to any fastingperiods within the initial monitoring period and determines a fastingvalue for a reference metric based on those fasting measurement valuescorresponding to fasting periods. Depending on the embodiment, thefasting reference value may be an average fasting glucose measurementvalue over the fasting periods within the initial monitoring period, anestimated amount of insulin needed for achieving a target glucose valuebased on the fasting glucose measurement values, or some other metricthat is a function of the glucose measurement values corresponding tothe fasting periods within the initial monitoring period.

After the initial monitoring period, the sensed glucose measurementvalues obtained by the infusion device during subsequent fasting periodsare utilized to determine an updated (or current) fasting value for thereference metric based on those recently sensed glucose measurementvalues that are coincident with, contemporaneous to, or otherwisetemporally correspond to a subsequent fasting period. The currentfasting value for the reference metric is compared to the fastingreference value determined based on the fasting sensor data from theinitial monitoring period, and in response to a deviation between thecurrent fasting value and the fasting reference value that exceeds athreshold, a notification is generated that indicates that the patientneeds to replace, rotate, inspect, or otherwise attend to the infusionset.

It should be noted that although the subject matter may be describedherein primarily in the context of the infusion device receiving andmonitoring measurement values, the subject matter is not necessarilylimited to implementation by the infusion device. In practice, thesubject matter may be implemented in an equivalent manner by any otherelectronic or computing device that is communicatively coupled to atleast one of the sensing arrangement and the infusion device and capableof receiving sensed measurement values for the patient as describedbelow.

Infusion System Overview

Turning now to FIG. 1, one exemplary embodiment of an infusion system100 includes, without limitation, a fluid infusion device (or infusionpump) 102, a sensing arrangement 104, a command control device (CCD)106, and a computer 108. The components of an infusion system 100 may berealized using different platforms, designs, and configurations, and theembodiment shown in FIG. 1 is not exhaustive or limiting. In practice,the infusion device 102 and the sensing arrangement 104 are secured atdesired locations on the body of a user (or patient), as illustrated inFIG. 1. In this regard, the locations at which the infusion device 102and the sensing arrangement 104 are secured to the body of the user inFIG. 1 are provided only as a representative, non-limiting, example. Theelements of the infusion system 100 may be similar to those described inU.S. Pat. No. 8,674,288, the subject matter of which is herebyincorporated by reference in its entirety.

In the illustrated embodiment of FIG. 1, the infusion device 102 isdesigned as a portable medical device suitable for infusing a fluid, aliquid, a gel, or other agent into the body of a user. In exemplaryembodiments, the infused fluid is insulin, although many other fluidsmay be administered through infusion such as, but not limited to, HIVdrugs, drugs to treat pulmonary hypertension, iron chelation drugs, painmedications, anti-cancer treatments, medications, vitamins, hormones, orthe like. In some embodiments, the fluid may include a nutritionalsupplement, a dye, a tracing medium, a saline medium, a hydrationmedium, or the like.

The sensing arrangement 104 generally represents the components of theinfusion system 100 configured to sense, detect, measure or otherwisequantify a condition of the user, and may include a sensor, a monitor,or the like, for providing data indicative of the condition that issensed, detected, measured or otherwise monitored by the sensingarrangement. In this regard, the sensing arrangement 104 may includeelectronics and enzymes reactive to a biological or physiologicalcondition of the user, such as a blood glucose level, or the like, andprovide data indicative of the blood glucose level to the infusiondevice 102, the CCD 106 and/or the computer 108. For example, theinfusion device 102, the CCD 106 and/or the computer 108 may include adisplay for presenting information or data to the user based on thesensor data received from the sensing arrangement 104, such as, forexample, a current glucose level of the user, a graph or chart of theuser's glucose level versus time, device status indicators, alertmessages, or the like. In other embodiments, the infusion device 102,the CCD 106 and/or the computer 108 may include electronics and softwarethat are configured to analyze sensor data and operate the infusiondevice 102 to deliver fluid to the body of the user based on the sensordata and/or preprogrammed delivery routines. Thus, in exemplaryembodiments, one or more of the infusion device 102, the sensingarrangement 104, the CCD 106, and/or the computer 108 includes atransmitter, a receiver, and/or other transceiver electronics that allowfor communication with other components of the infusion system 100, sothat the sensing arrangement 104 may transmit sensor data or monitordata to one or more of the infusion device 102, the CCD 106 and/or thecomputer 108.

Still referring to FIG. 1, in various embodiments, the sensingarrangement 104 may be secured to the body of the user or embedded inthe body of the user at a location that is remote from the location atwhich the infusion device 102 is secured to the body of the user. Invarious other embodiments, the sensing arrangement 104 may beincorporated within the infusion device 102. In other embodiments, thesensing arrangement 104 may be separate and apart from the infusiondevice 102, and may be, for example, part of the CCD 106. In suchembodiments, the sensing arrangement 104 may be configured to receive abiological sample, analyte, or the like, to measure a condition of theuser.

In various embodiments, the CCD 106 and/or the computer 108 may includeelectronics and other components configured to perform processing,delivery routine storage, and to control the infusion device 102 in amanner that is influenced by sensor data measured by and/or receivedfrom the sensing arrangement 104. By including control functions in theCCD 106 and/or the computer 108, the infusion device 102 may be madewith more simplified electronics. However, in other embodiments, theinfusion device 102 may include all control functions, and may operatewithout the CCD 106 and/or the computer 108. In various embodiments, theCCD 106 may be a portable electronic device. In addition, in variousembodiments, the infusion device 102 and/or the sensing arrangement 104may be configured to transmit data to the CCD 106 and/or the computer108 for display or processing of the data by the CCD 106 and/or thecomputer 108.

In some embodiments, the CCD 106 and/or the computer 108 may provideinformation to the user that facilitates the user's subsequent use ofthe infusion device 102. For example, the CCD 106 may provideinformation to the user to allow the user to determine the rate or doseof medication to be administered into the user's body. In otherembodiments, the CCD 106 may provide information to the infusion device102 to autonomously control the rate or dose of medication administeredinto the body of the user. In some embodiments, the sensing arrangement104 may be integrated into the CCD 106. Such embodiments may allow theuser to monitor a condition by providing, for example, a sample of hisor her blood to the sensing arrangement 104 to assess his or hercondition. In some embodiments, the sensing arrangement 104 and the CCD106 may be used for determining glucose levels in the blood and/or bodyfluids of the user without the use of, or necessity of, a wire or cableconnection between the infusion device 102 and the sensing arrangement104 and/or the CCD 106.

In one or more exemplary embodiments, the sensing arrangement 104 and/orthe infusion device 102 are cooperatively configured to utilize aclosed-loop system for delivering fluid to the user. Examples of sensingdevices and/or infusion pumps utilizing closed-loop systems may be foundat, but are not limited to, the following U.S. Pat. Nos. 6,088,608,6,119,028, 6,589,229, 6,740,072, 6,827,702, 7,323,142, and 7,402,153,all of which are incorporated herein by reference in their entirety. Insuch embodiments, the sensing arrangement 104 is configured to sense ormeasure a condition of the user, such as, blood glucose level or thelike. The infusion device 102 is configured to deliver fluid in responseto the condition sensed by the sensing arrangement 104. In turn, thesensing arrangement 104 continues to sense or otherwise quantify acurrent condition of the user, thereby allowing the infusion device 102to deliver fluid continuously in response to the condition currently (ormost recently) sensed by the sensing arrangement 104 indefinitely. Insome embodiments, the sensing arrangement 104 and/or the infusion device102 may be configured to utilize the closed-loop system only for aportion of the day, for example only when the user is asleep or awake.

FIGS. 2-4 depict one exemplary embodiment of a fluid infusion device 200(or alternatively, infusion pump) suitable for use in an infusionsystem, such as, for example, as infusion device 102 in the infusionsystem 100 of FIG. 1. The fluid infusion device 200 is a portablemedical device designed to be carried or worn by a patient (or user),and the fluid infusion device 200 may leverage any number ofconventional features, components, elements, and characteristics ofexisting fluid infusion devices, such as, for example, some of thefeatures, components, elements, and/or characteristics described in U.S.Pat. Nos. 6,485,465 and 7,621,893. It should be appreciated that FIGS.2-4 depict some aspects of the infusion device 200 in a simplifiedmanner; in practice, the infusion device 200 could include additionalelements, features, or components that are not shown or described indetail herein.

As best illustrated in FIGS. 2-3, the illustrated embodiment of thefluid infusion device 200 includes a housing 202 adapted to receive afluid-containing reservoir 205. An opening 220 in the housing 202accommodates a fitting 223 (or cap) for the reservoir 205, with thefitting 223 being configured to mate or otherwise interface with tubing221 of an infusion set 225 that provides a fluid path to/from the bodyof the user. In this manner, fluid communication from the interior ofthe reservoir 205 to the user is established via the tubing 221. Theillustrated fluid infusion device 200 includes a human-machine interface(HMI) 230 (or user interface) that includes elements 232, 234 that canbe manipulated by the user to administer a bolus of fluid (e.g.,insulin), to change therapy settings, to change user preferences, toselect display features, and the like. The infusion device also includesa display element 226, such as a liquid crystal display (LCD) or anothersuitable display element, that can be used to present various types ofinformation or data to the user, such as, without limitation: thecurrent glucose level of the patient; the time; a graph or chart of thepatient's glucose level versus time; device status indicators; etc.

The housing 202 is formed from a substantially rigid material having ahollow interior 214 adapted to allow an electronics assembly 204, asliding member (or slide) 206, a drive system 208, a sensor assembly210, and a drive system capping member 212 to be disposed therein inaddition to the reservoir 205, with the contents of the housing 202being enclosed by a housing capping member 216. The opening 220, theslide 206, and the drive system 208 are coaxially aligned in an axialdirection (indicated by arrow 218), whereby the drive system 208facilitates linear displacement of the slide 206 in the axial direction218 to dispense fluid from the reservoir 205 (after the reservoir 205has been inserted into opening 220), with the sensor assembly 210 beingconfigured to measure axial forces (e.g., forces aligned with the axialdirection 218) exerted on the sensor assembly 210 responsive tooperating the drive system 208 to displace the slide 206. In variousembodiments, the sensor assembly 210 may be utilized to detect one ormore of the following: an occlusion in a fluid path that slows,prevents, or otherwise degrades fluid delivery from the reservoir 205 toa user's body; when the reservoir 205 is empty; when the slide 206 isproperly seated with the reservoir 205; when a fluid dose has beendelivered; when the infusion pump 200 is subjected to shock orvibration; when the infusion pump 200 requires maintenance.

Depending on the embodiment, the fluid-containing reservoir 205 may berealized as a syringe, a vial, a cartridge, a bag, or the like. Incertain embodiments, the infused fluid is insulin, although many otherfluids may be administered through infusion such as, but not limited to,HIV drugs, drugs to treat pulmonary hypertension, iron chelation drugs,pain medications, anti-cancer treatments, medications, vitamins,hormones, or the like. As best illustrated in FIGS. 3-4, the reservoir205 typically includes a reservoir barrel 219 that contains the fluidand is concentrically and/or coaxially aligned with the slide 206 (e.g.,in the axial direction 218) when the reservoir 205 is inserted into theinfusion pump 200. The end of the reservoir 205 proximate the opening220 may include or otherwise mate with the fitting 223, which securesthe reservoir 205 in the housing 202 and prevents displacement of thereservoir 205 in the axial direction 218 with respect to the housing 202after the reservoir 205 is inserted into the housing 202. As describedabove, the fitting 223 extends from (or through) the opening 220 of thehousing 202 and mates with tubing 221 to establish fluid communicationfrom the interior of the reservoir 205 (e.g., reservoir barrel 219) tothe user via the tubing 221 and infusion set 225. The opposing end ofthe reservoir 205 proximate the slide 206 includes a plunger 217 (orstopper) positioned to push fluid from inside the barrel 219 of thereservoir 205 along a fluid path through tubing 221 to a user. The slide206 is configured to mechanically couple or otherwise engage with theplunger 217, thereby becoming seated with the plunger 217 and/orreservoir 205. Fluid is forced from the reservoir 205 via tubing 221 asthe drive system 208 is operated to displace the slide 206 in the axialdirection 218 toward the opening 220 in the housing 202.

In the illustrated embodiment of FIGS. 3-4, the drive system 208includes a motor assembly 207 and a drive screw 209. The motor assembly207 includes a motor that is coupled to drive train components of thedrive system 208 that are configured to convert rotational motor motionto a translational displacement of the slide 206 in the axial direction218, and thereby engaging and displacing the plunger 217 of thereservoir 205 in the axial direction 218. In some embodiments, the motorassembly 207 may also be powered to translate the slide 206 in theopposing direction (e.g., the direction opposite direction 218) toretract and/or detach from the reservoir 205 to allow the reservoir 205to be replaced. In exemplary embodiments, the motor assembly 207includes a brushless DC (BLDC) motor having one or more permanentmagnets mounted, affixed, or otherwise disposed on its rotor. However,the subject matter described herein is not necessarily limited to usewith BLDC motors, and in alternative embodiments, the motor may berealized as a solenoid motor, an AC motor, a stepper motor, apiezoelectric caterpillar drive, a shape memory actuator drive, anelectrochemical gas cell, a thermally driven gas cell, a bimetallicactuator, or the like. The drive train components may comprise one ormore lead screws, cams, ratchets, jacks, pulleys, pawls, clamps, gears,nuts, slides, bearings, levers, beams, stoppers, plungers, sliders,brackets, guides, bearings, supports, bellows, caps, diaphragms, bags,heaters, or the like. In this regard, although the illustratedembodiment of the infusion pump utilizes a coaxially aligned drivetrain, the motor could be arranged in an offset or otherwise non-coaxialmanner, relative to the longitudinal axis of the reservoir 205.

As best shown in FIG. 4, the drive screw 209 mates with threads 402internal to the slide 206. When the motor assembly 207 is powered andoperated, the drive screw 209 rotates, and the slide 206 is forced totranslate in the axial direction 218. In an exemplary embodiment, theinfusion pump 200 includes a sleeve 211 to prevent the slide 206 fromrotating when the drive screw 209 of the drive system 208 rotates. Thus,rotation of the drive screw 209 causes the slide 206 to extend orretract relative to the drive motor assembly 207. When the fluidinfusion device is assembled and operational, the slide 206 contacts theplunger 217 to engage the reservoir 205 and control delivery of fluidfrom the infusion pump 200. In an exemplary embodiment, the shoulderportion 215 of the slide 206 contacts or otherwise engages the plunger217 to displace the plunger 217 in the axial direction 218. Inalternative embodiments, the slide 206 may include a threaded tip 213capable of being detachably engaged with internal threads 404 on theplunger 217 of the reservoir 205, as described in detail in U.S. Pat.Nos. 6,248,093 and 6,485,465, which are incorporated by referenceherein.

As illustrated in FIG. 3, the electronics assembly 204 includes controlelectronics 224 coupled to the display element 226, with the housing 202including a transparent window portion 228 that is aligned with thedisplay element 226 to allow the display 226 to be viewed by the userwhen the electronics assembly 204 is disposed within the interior 214 ofthe housing 202. The control electronics 224 generally represent thehardware, firmware, processing logic and/or software (or combinationsthereof) configured to control operation of the motor assembly 207and/or drive system 208, as described in greater detail below in thecontext of FIG. 5. Whether such functionality is implemented ashardware, firmware, a state machine, or software depends upon theparticular application and design constraints imposed on the embodiment.Those familiar with the concepts described here may implement suchfunctionality in a suitable manner for each particular application, butsuch implementation decisions should not be interpreted as beingrestrictive or limiting. In an exemplary embodiment, the controlelectronics 224 includes one or more programmable controllers that maybe programmed to control operation of the infusion pump 200.

The motor assembly 207 includes one or more electrical leads 236 adaptedto be electrically coupled to the electronics assembly 204 to establishcommunication between the control electronics 224 and the motor assembly207. In response to command signals from the control electronics 224that operate a motor driver (e.g., a power converter) to regulate theamount of power supplied to the motor from a power supply, the motoractuates the drive train components of the drive system 208 to displacethe slide 206 in the axial direction 218 to force fluid from thereservoir 205 along a fluid path (including tubing 221 and an infusionset), thereby administering doses of the fluid contained in thereservoir 205 into the user's body. Preferably, the power supply isrealized one or more batteries contained within the housing 202.Alternatively, the power supply may be a solar panel, capacitor, AC orDC power supplied through a power cord, or the like. In someembodiments, the control electronics 224 may operate the motor of themotor assembly 207 and/or drive system 208 in a stepwise manner,typically on an intermittent basis; to administer discrete precise dosesof the fluid to the user according to programmed delivery profiles.

Referring to FIGS. 2-4, as described above, the user interface 230includes HMI elements, such as buttons 232 and a directional pad 234,that are formed on a graphic keypad overlay 231 that overlies a keypadassembly 233, which includes features corresponding to the buttons 232,directional pad 234 or other user interface items indicated by thegraphic keypad overlay 231. When assembled, the keypad assembly 233 iscoupled to the control electronics 224, thereby allowing the HMIelements 232, 234 to be manipulated by the user to interact with thecontrol electronics 224 and control operation of the infusion pump 200,for example, to administer a bolus of insulin, to change therapysettings, to change user preferences, to select display features, to setor disable alarms and reminders, and the like. In this regard, thecontrol electronics 224 maintains and/or provides information to thedisplay 226 regarding program parameters, delivery profiles, pumpoperation, alarms, warnings, statuses, or the like, which may beadjusted using the HMI elements 232, 234. In various embodiments, theHMI elements 232, 234 may be realized as physical objects (e.g.,buttons, knobs, joysticks, and the like) or virtual objects (e.g., usingtouch-sensing and/or proximity-sensing technologies). For example, insome embodiments, the display 226 may be realized as a touch screen ortouch-sensitive display, and in such embodiments, the features and/orfunctionality of the HMI elements 232, 234 may be integrated into thedisplay 226 and the HMI 230 may not be present. In some embodiments, theelectronics assembly 204 may also include alert generating elementscoupled to the control electronics 224 and suitably configured togenerate one or more types of feedback, such as, without limitation:audible feedback; visual feedback; haptic (physical) feedback; or thelike.

Referring to FIGS. 3-4, in accordance with one or more embodiments, thesensor assembly 210 includes a back plate structure 250 and a loadingelement 260. The loading element 260 is disposed between the cappingmember 212 and a beam structure 270 that includes one or more beamshaving sensing elements disposed thereon that are influenced bycompressive force applied to the sensor assembly 210 that deflects theone or more beams, as described in greater detail in U.S. Pat. No.8,474,332, which is incorporated by reference herein. In exemplaryembodiments, the back plate structure 250 is affixed, adhered, mounted,or otherwise mechanically coupled to the bottom surface 238 of the drivesystem 208 such that the back plate structure 250 resides between thebottom surface 238 of the drive system 208 and the housing cap 216. Thedrive system capping member 212 is contoured to accommodate and conformto the bottom of the sensor assembly 210 and the drive system 208. Thedrive system capping member 212 may be affixed to the interior of thehousing 202 to prevent displacement of the sensor assembly 210 in thedirection opposite the direction of force provided by the drive system208 (e.g., the direction opposite direction 218). Thus, the sensorassembly 210 is positioned between the motor assembly 207 and secured bythe capping member 212, which prevents displacement of the sensorassembly 210 in a downward direction opposite the direction of arrow218, such that the sensor assembly 210 is subjected to a reactionarycompressive force when the drive system 208 and/or motor assembly 207 isoperated to displace the slide 206 in the axial direction 218 inopposition to the fluid pressure in the reservoir 205. Under normaloperating conditions, the compressive force applied to the sensorassembly 210 is correlated with the fluid pressure in the reservoir 205.As shown, electrical leads 240 are adapted to electrically couple thesensing elements of the sensor assembly 210 to the electronics assembly204 to establish communication to the control electronics 224, whereinthe control electronics 224 are configured to measure, receive, orotherwise obtain electrical signals from the sensing elements of thesensor assembly 210 that are indicative of the force applied by thedrive system 208 in the axial direction 218.

FIG. 5 depicts an exemplary embodiment of a control system 500 suitablefor use with an infusion device 502, such as the infusion device 102 inFIG. 1 or the infusion device 200 of FIG. 2. The control system 500 iscapable of controlling or otherwise regulating a physiological conditionin the body 501 of a user to a desired (or target) value or otherwisemaintain the condition within a range of acceptable values in anautomated or autonomous manner. In one or more exemplary embodiments,the condition being regulated is sensed, detected, measured or otherwisequantified by a sensing arrangement 504 (e.g., sensing arrangement 104)communicatively coupled to the infusion device 502. However, it shouldbe noted that in alternative embodiments, the condition being regulatedby the control system 500 may be correlative to the measured valuesobtained by the sensing arrangement 504. That said, for clarity andpurposes of explanation, the subject matter may be described herein inthe context of the sensing arrangement 504 being realized as a glucosesensing arrangement that senses, detects, measures or otherwisequantifies the user's glucose level, which is being regulated in thebody 501 of the user by the control system 500.

In exemplary embodiments, the sensing arrangement 504 includes one ormore interstitial glucose sensing elements that generate or otherwiseoutput electrical signals having a signal characteristic that iscorrelative to, influenced by, or otherwise indicative of the relativeinterstitial fluid glucose level in the body 501 of the user. The outputelectrical signals are filtered or otherwise processed to obtain ameasurement value indicative of the user's interstitial fluid glucoselevel. In exemplary embodiments, a blood glucose meter 530, such as afinger stick device, is utilized to directly sense, detect, measure orotherwise quantify the blood glucose in the body 501 of the user. Inthis regard, the blood glucose meter 530 outputs or otherwise provides ameasured blood glucose value that may be utilized as a referencemeasurement for calibrating the sensing arrangement 504 and converting ameasurement value indicative of the user's interstitial fluid glucoselevel into a corresponding calibrated blood glucose value. For purposesof explanation, a blood glucose value calculated based on the electricalsignals output by the sensing element(s) of the sensing arrangement 504may alternatively be referred to herein as the sensor glucose value, thesensed glucose value, or variants thereof.

In the illustrated embodiment, the pump control system 520 generallyrepresents the electronics and other components of the infusion device502 that control operation of the fluid infusion device 502 according toa desired infusion delivery program in a manner that is influenced bythe sensed glucose value indicative of a current glucose level in thebody 501 of the user. For example, to support a closed-loop operatingmode, the pump control system 520 maintains, receives, or otherwiseobtains a target or commanded glucose value, and automatically generatesor otherwise determines dosage commands for operating an actuationarrangement, such as a motor 507, to displace the plunger 517 (e.g., viaa drive system 508) and deliver insulin to the body 501 of the userbased on the difference between a sensed glucose value and the targetglucose value. In other operating modes, the pump control system 520 maygenerate or otherwise determine dosage commands configured to maintainthe sensed glucose value below an upper glucose limit, above a lowerglucose limit, or otherwise within a desired range of glucose values. Inpractice, the infusion device 502 may store or otherwise maintain thetarget value, upper and/or lower glucose limit(s), and/or other glucosethreshold value(s) in a data storage element accessible to the pumpcontrol system 520.

The target glucose value and other threshold glucose values may bereceived from an external component (e.g., CCD 106 and/or computingdevice 108) or be input by a user via a user interface element 540associated with the infusion device 502. In practice, the one or moreuser interface element(s) 540 associated with the infusion device 502typically include at least one input user interface element, such as,for example, a button, a keypad, a keyboard, a knob, a joystick, amouse, a touch panel, a touchscreen, a microphone or another audio inputdevice, and/or the like. Additionally, the one or more user interfaceelement(s) 540 include at least one output user interface element, suchas, for example, a display element (e.g., a light-emitting diode or thelike), a display device (e.g., a liquid crystal display or the like), aspeaker or another audio output device, a haptic feedback device, or thelike, for providing notifications or other information to the user. Itshould be noted that although FIG. 5 depicts the user interfaceelement(s) 540 as being separate from the infusion device 502, inpractice, one or more of the user interface element(s) 540 may beintegrated with the infusion device 502. Furthermore, in someembodiments, one or more user interface element(s) 540 are integratedwith the sensing arrangement 504 in addition to and/or in alternative tothe user interface element(s) 540 integrated with the infusion device502. The user interface element(s) 540 may be manipulated by the user tooperate the infusion device 502 to deliver correction boluses, adjusttarget and/or threshold values, modify the delivery control scheme oroperating mode, and the like, as desired.

Still referring to FIG. 5, in the illustrated embodiment, the infusiondevice 502 includes a motor control module 512 coupled to a motor 507(e.g., motor assembly 207) that is operable to displace a plunger 517(e.g., plunger 217) in a reservoir (e.g., reservoir 205) and provide adesired amount of fluid to the body 501 of a user. In this regard,displacement of the plunger 517 results in the delivery of a fluid thatis capable of influencing the condition in the body 501 of the user tothe body 501 of the user via a fluid delivery path (e.g., via tubing 221of an infusion set 225). A motor driver module 514 is coupled between anenergy source 503 and the motor 507. The motor control module 512 iscoupled to the motor driver module 514, and the motor control module 512generates or otherwise provides command signals that operate the motordriver module 514 to provide current (or power) from the energy source503 to the motor 507 to displace the plunger 517 in response toreceiving, from a pump control system 520, a dosage command indicativeof the desired amount of fluid to be delivered.

In exemplary embodiments, the energy source 503 is realized as a batteryhoused within the infusion device 502 (e.g., within housing 202) thatprovides direct current (DC) power. In this regard, the motor drivermodule 514 generally represents the combination of circuitry, hardwareand/or other electrical components configured to convert or otherwisetransfer DC power provided by the energy source 503 into alternatingelectrical signals applied to respective phases of the stator windingsof the motor 507 that result in current flowing through the statorwindings that generates a stator magnetic field and causes the rotor ofthe motor 507 to rotate. The motor control module 512 is configured toreceive or otherwise obtain a commanded dosage from the pump controlsystem 520, convert the commanded dosage to a commanded translationaldisplacement of the plunger 517, and command, signal, or otherwiseoperate the motor driver module 514 to cause the rotor of the motor 507to rotate by an amount that produces the commanded translationaldisplacement of the plunger 517. For example, the motor control module512 may determine an amount of rotation of the rotor required to producetranslational displacement of the plunger 517 that achieves thecommanded dosage received from the pump control system 520. Based on thecurrent rotational position (or orientation) of the rotor with respectto the stator that is indicated by the output of the rotor sensingarrangement 516, the motor control module 512 determines the appropriatesequence of alternating electrical signals to be applied to therespective phases of the stator windings that should rotate the rotor bythe determined amount of rotation from its current position (ororientation). In embodiments where the motor 507 is realized as a BLDCmotor, the alternating electrical signals commutate the respectivephases of the stator windings at the appropriate orientation of therotor magnetic poles with respect to the stator and in the appropriateorder to provide a rotating stator magnetic field that rotates the rotorin the desired direction. Thereafter, the motor control module 512operates the motor driver module 514 to apply the determined alternatingelectrical signals (e.g., the command signals) to the stator windings ofthe motor 507 to achieve the desired delivery of fluid to the user.

When the motor control module 512 is operating the motor driver module514, current flows from the energy source 503 through the statorwindings of the motor 507 to produce a stator magnetic field thatinteracts with the rotor magnetic field. In some embodiments, after themotor control module 512 operates the motor driver module 514 and/ormotor 507 to achieve the commanded dosage, the motor control module 512ceases operating the motor driver module 514 and/or motor 507 until asubsequent dosage command is received. In this regard, the motor drivermodule 514 and the motor 507 enter an idle state during which the motordriver module 514 effectively disconnects or isolates the statorwindings of the motor 507 from the energy source 503. In other words,current does not flow from the energy source 503 through the statorwindings of the motor 507 when the motor 507 is idle, and thus, themotor 507 does not consume power from the energy source 503 in the idlestate, thereby improving efficiency.

Depending on the embodiment, the motor control module 512 may beimplemented or realized with a general purpose processor, amicroprocessor, a controller, a microcontroller, a state machine, acontent addressable memory, an application specific integrated circuit,a field programmable gate array, any suitable programmable logic device,discrete gate or transistor logic, discrete hardware components, or anycombination thereof, designed to perform the functions described herein.In exemplary embodiments, the motor control module 512 includes orotherwise accesses a data storage element or memory, including any sortof random access memory (RAM), read only memory (ROM), flash memory,registers, hard disks, removable disks, magnetic or optical massstorage, or any other short or long term storage media or othernon-transitory computer-readable medium, which is capable of storingprogramming instructions for execution by the motor control module 512.The computer-executable programming instructions, when read and executedby the motor control module 512, cause the motor control module 512 toperform or otherwise support the tasks, operations, functions, andprocesses described herein.

It should be appreciated that FIG. 5 is a simplified representation ofthe infusion device 502 for purposes of explanation and is not intendedto limit the subject matter described herein in any way. In this regard,depending on the embodiment, some features and/or functionality of thesensing arrangement 504 may implemented by or otherwise integrated intothe pump control system 520, or vice versa. Similarly, in practice, thefeatures and/or functionality of the motor control module 512 mayimplemented by or otherwise integrated into the pump control system 520,or vice versa. Furthermore, the features and/or functionality of thepump control system 520 may be implemented by control electronics 224located in the fluid infusion device 200, 400, while in alternativeembodiments, the pump control system 520 may be implemented by a remotecomputing device that is physically distinct and/or separate from theinfusion device 502, such as, for example, the CCD 106 or the computingdevice 108.

FIG. 6 depicts an exemplary embodiment of a pump control system 600suitable for use as the pump control system 520 in FIG. 5 in accordancewith one or more embodiments. The illustrated pump control system 600includes, without limitation, a pump control module 602, acommunications interface 604, and a data storage element (or memory)606. The pump control module 602 is coupled to the communicationsinterface 604 and the memory 606, and the pump control module 602 issuitably configured to support the operations, tasks, and/or processesdescribed herein. In exemplary embodiments, the pump control module 602is also coupled to one or more user interface elements 608 (e.g., userinterface 230, 540) for receiving user input and providingnotifications, alerts, or other therapy information to the user.Although FIG. 6 depicts the user interface element 608 as being separatefrom the pump control system 600, in various alternative embodiments,the user interface element 608 may be integrated with the pump controlsystem 600 (e.g., as part of the infusion device 200, 502), the sensingarrangement 504 or another element of an infusion system 100 (e.g., thecomputer 108 or CCD 106).

Referring to FIG. 6 and with reference to FIG. 5, the communicationsinterface 604 generally represents the hardware, circuitry, logic,firmware and/or other components of the pump control system 600 that arecoupled to the pump control module 602 and configured to supportcommunications between the pump control system 600 and the sensingarrangement 504. In this regard, the communications interface 604 mayinclude or otherwise be coupled to one or more transceiver modulescapable of supporting wireless communications between the pump controlsystem 520, 600 and the sensing arrangement 504 or another electronicdevice 106, 108 in an infusion system 100. In other embodiments, thecommunications interface 604 may be configured to support wiredcommunications to/from the sensing arrangement 504.

The pump control module 602 generally represents the hardware,circuitry, logic, firmware and/or other component of the pump controlsystem 600 that is coupled to the communications interface 604 andconfigured to determine dosage commands for operating the motor 506 todeliver fluid to the body 501 based on data received from the sensingarrangement 504 and perform various additional tasks, operations,functions and/or operations described herein. For example, in exemplaryembodiments, pump control module 602 implements or otherwise executes acommand generation application 610 that supports one or more autonomousoperating modes and calculates or otherwise determines dosage commandsfor operating the motor 506 of the infusion device 502 in an autonomousoperating mode based at least in part on a current measurement value fora condition in the body 501 of the user. Additionally, in exemplaryembodiments described herein, the pump control module 602 alsoimplements or otherwise executes an insertion site monitoringapplication 612 that supports monitoring sensed glucose measurementvalues received via the sensing arrangement 504, analyzing the efficacyof the current infusion set or current insertion site based on thesensed glucose measurement values, and generating user notifications oralerts provided to the patient or user via the user interface element608, as described in greater detail below in the context of FIGS. 8-9.

Still referring to FIG. 6, in a closed-loop operating mode, the commandgeneration application 610 may determine a dosage command for operatingthe motor 506 to deliver insulin to the body 501 of the user based atleast in part on the current glucose measurement value most recentlyreceived from the sensing arrangement 504 to regulate the user's bloodglucose level to a target reference glucose value. Additionally, thecommand generation application 610 may generate dosage commands forboluses that are manually-initiated or otherwise instructed by a uservia a user interface element 608. For example, regardless of theoperating mode being implemented, the command generation application 610may determine a dosage command for operating the motor 506 to deliver abolus of insulin to the body 501 of the user that corresponds to acorrection bolus or meal bolus amount selected or otherwise indicated bythe user via the user interface element 230, 540, 608.

Depending on the embodiment, the pump control module 602 may beimplemented or realized with a general purpose processor, amicroprocessor, a controller, a microcontroller, a state machine, acontent addressable memory, an application specific integrated circuit,a field programmable gate array, any suitable programmable logic device,discrete gate or transistor logic, discrete hardware components, or anycombination thereof, designed to perform the functions described herein.In this regard, the steps of a method or algorithm described inconnection with the embodiments disclosed herein may be embodieddirectly in hardware, in firmware, in a software module executed by thepump control module 602, or in any practical combination thereof. Inexemplary embodiments, the pump control module 602 includes or otherwiseaccesses the data storage element or memory 606, which may be realizedusing any sort of non-transitory computer-readable medium capable ofstoring programming instructions for execution by the pump controlmodule 602. The computer-executable programming instructions, when readand executed by the pump control module 602, cause the pump controlmodule 602 to implement or otherwise generate the applications 610, 612and perform the tasks, operations, functions, and processes described ingreater detail below.

It should be understood that FIG. 6 is a simplified representation of apump control system 600 for purposes of explanation and is not intendedto limit the subject matter described herein in any way. For example, insome embodiments, the features and/or functionality of the motor controlmodule 512 may be implemented by or otherwise integrated into the pumpcontrol system 600 and/or the pump control module 602, for example, bythe command generation application 610 converting the dosage commandinto a corresponding motor command, in which case, the separate motorcontrol module 512 may be absent from an embodiment of the infusiondevice 502.

FIG. 7 depicts an exemplary closed-loop control system 700 that may beimplemented by a pump control system 520, 600 to provide a closed-loopoperating mode that autonomously regulates a condition in the body of auser to a reference (or target) value. It should be appreciated thatFIG. 7 is a simplified representation of the control system 700 forpurposes of explanation and is not intended to limit the subject matterdescribed herein in any way.

In exemplary embodiments, the control system 700 receives or otherwiseobtains a target glucose value at input 702. In some embodiments, thetarget glucose value may be stored or otherwise maintained by theinfusion device 502 (e.g., in memory 606), however, in some alternativeembodiments, the target value may be received from an external component(e.g., CCD 106 and/or computer 108). In one or more embodiments, thetarget glucose value may be dynamically calculated or otherwisedetermined prior to entering the closed-loop operating mode based on oneor more patient-specific control parameters. For example, the targetblood glucose value may be calculated based at least in part on apatient-specific reference basal rate and a patient-specific dailyinsulin requirement, which are determined based on historical deliveryinformation over a preceding interval of time (e.g., the amount ofinsulin delivered over the preceding 24 hours). The control system 700also receives or otherwise obtains a current glucose measurement value(e.g., the most recently obtained sensor glucose value) from the sensingarrangement 504 at input 704. The illustrated control system 700implements or otherwise provides proportional-integral-derivative (PID)control to determine or otherwise generate delivery commands foroperating the motor 510 based at least in part on the difference betweenthe target glucose value and the current glucose measurement value. Inthis regard, the PID control attempts to minimize the difference betweenthe measured value and the target value, and thereby regulates themeasured value to the desired value. PID control parameters are appliedto the difference between the target glucose level at input 702 and themeasured glucose level at input 704 to generate or otherwise determine adosage (or delivery) command provided at output 730. Based on thatdelivery command, the motor control module 512 operates the motor 510 todeliver insulin to the body of the user to influence the user's glucoselevel, and thereby reduce the difference between a subsequently measuredglucose level and the target glucose level.

The illustrated control system 700 includes or otherwise implements asummation block 706 configured to determine a difference between thetarget value obtained at input 702 and the measured value obtained fromthe sensing arrangement 504 at input 704, for example, by subtractingthe target value from the measured value. The output of the summationblock 706 represents the difference between the measured and targetvalues, which is then provided to each of a proportional term path, anintegral term path, and a derivative term path. The proportional termpath includes a gain block 720 that multiplies the difference by aproportional gain coefficient, K_(P), to obtain the proportional term.The integral term path includes an integration block 708 that integratesthe difference and a gain block 722 that multiplies the integrateddifference by an integral gain coefficient, K_(I), to obtain theintegral term. The derivative term path includes a derivative block 710that determines the derivative of the difference and a gain block 724that multiplies the derivative of the difference by a derivative gaincoefficient, K_(D), to obtain the derivative term. The proportionalterm, the integral term, and the derivative term are then added orotherwise combined to obtain a delivery command that is utilized tooperate the motor at output 730. Various implementation detailspertaining to closed-loop PID control and determine gain coefficientsare described in greater detail in U.S. Pat. No. 7,402,153, which isincorporated by reference.

In one or more exemplary embodiments, the PID gain coefficients areuser-specific (or patient-specific) and dynamically calculated orotherwise determined prior to entering the closed-loop operating modebased on historical insulin delivery information (e.g., amounts and/ortimings of previous dosages, historical correction bolus information, orthe like), historical sensor measurement values, historical referenceblood glucose measurement values, user-reported or user-input events(e.g., meals, exercise, and the like), and the like. In this regard, oneor more patient-specific control parameters (e.g., an insulinsensitivity factor, a daily insulin requirement, an insulin limit, areference basal rate, a reference fasting glucose, an active insulinaction duration, pharmodynamical time constants, or the like) may beutilized to compensate, correct, or otherwise adjust the PID gaincoefficients to account for various operating conditions experiencedand/or exhibited by the infusion device 502. The PID gain coefficientsmay be maintained by the memory 606 accessible to the pump controlmodule 602. In this regard, the memory 606 may include a plurality ofregisters associated with the control parameters for the PID control.For example, a first parameter register may store the target glucosevalue and be accessed by or otherwise coupled to the summation block 706at input 702, and similarly, a second parameter register accessed by theproportional gain block 720 may store the proportional gain coefficient,a third parameter register accessed by the integration gain block 722may store the integration gain coefficient, and a fourth parameterregister accessed by the derivative gain block 724 may store thederivative gain coefficient.

Insertion Site Loss Detection

As described above, in exemplary embodiments described herein,measurement values from a sensing arrangement 104, 504 are utilized todetermine whether an insertion site loss has occurred and providecorresponding notifications regarding use of the current infusion setand/or the current insertion site. In this regard, insertion site lossshould be understood as referring to a condition where sensed glucosemeasurement values indicate the effectiveness of the currentconfiguration of infusion set and insertion site has decreased to thepoint that a new infusion set and/or new insertion site should beutilized to avoid potential adverse events. For example, in response todetecting an insertion site loss condition, an infusion device 102, 502may generate an alert that indicates that the infusion set 225 should bereplaced and rotated to a new insertion site.

It should be noted that insertion site notifications may be providedusing any number of devices of an infusion system 100, 500. For example,one or more graphical user interface (GUI) notifications may begenerated or provided on any one of the infusion device 102, 200, 502(e.g., display element 226, user interface element 540, 608, or thelike), the sensing arrangement 104, 504, the computer 106, and/or theCCD 108. That said, for purposes of explanation, the subject matter maybe described herein primarily in the context of the pump control system520, 600 of the infusion device 102, 200, 502 generating the insertionsite notifications; however, it should be appreciated that variousaspects of the processes described below in the context of FIGS. 8-9could be implemented or supported by any number of the other electronicdevices in an infusion system 100, 500, and the subject matter describedherein is not necessarily limited to implementation by an infusiondevice 102, 200, 502.

FIG. 8 depicts an exemplary site monitoring process 800 suitable forimplementation by a control system associated with an electronic device,such as a control system 520, 600 in an infusion device 102, 200, 502,to establish a fasting reference value for use in detecting an insertionsite loss condition, as described in greater detail below in the contextof FIG. 9. The various tasks performed in connection with the sitemonitoring process 800 may be performed by hardware, firmware, softwareexecuted by processing circuitry, or any combination thereof. Forillustrative purposes, the following description refers to elementsmentioned above in connection with FIGS. 1-7. In practice, portions ofthe site monitoring process 800 may be performed by different elementsof an infusion system, however, for purposes of explanation, the sitemonitoring process 800 may be described herein primarily in the contextof the infusion device 502, the pump control system 520, 600, and/or thepump control module 602. It should be appreciated that the sitemonitoring process 800 may include any number of additional oralternative tasks, the tasks need not be performed in the illustratedorder and/or the tasks may be performed concurrently, and/or the sitemonitoring process 800 may be incorporated into a more comprehensiveprocedure or process having additional functionality not described indetail herein. Moreover, one or more of the tasks shown and described inthe context of FIG. 8 could be omitted from a practical embodiment ofthe site monitoring process 800 as long as the intended overallfunctionality remains intact.

In exemplary embodiments, the site monitoring process 800 is performedwhenever a new infusion set is initialized and inserted in the body of apatient at an insertion site. The site monitoring process 800 monitorssensed measurement values during an initial monitoring periodcorresponding to an initial phase of the lifetime of the infusion set(e.g., the first 48 hours or the like), detects or identifies fastingconditions during that initial monitoring period, and then determines afasting reference value for the infusion set based on the sensedmeasurement values coincident with, concurrent to, or otherwisetemporally corresponding to fasting periods during the initialmonitoring period. As described in greater detail below, a fastingperiod should be understood as referring to a window of time duringwhich a fasting condition exists and the sensed glucose measurementvalues are relatively steady and not overly susceptible to variationsdue to insulin that remains active in the body of the patient.

The site monitoring process 800 detects or otherwise identifies afasting condition by verifying or otherwise identifying when delivery offluid by an infusion device is not currently suspended, when there areno active alerts or notification, and when a meal or bolus has notoccurred within a threshold period of time (tasks 802, 804, 806, 808).In this regard, the monitoring application 612 may interact with one ormore of the command generation application 610, the memory 606, and/oranother application or process executed by the pump control module 602to obtain information or data characterizing current delivery status andverify that the delivery of fluid is not currently suspended. Forexample, the monitoring application 612 may monitor a flag bit having avalue that is set by the command generation application 610 to indicatewhether the delivery is enabled (e.g., a logical low or ‘0’ bit value)or suspended (e.g., a logical high or ‘1’ bit value). After verifyingdelivery is not suspended, the monitoring application 612 may similarlyinteract with one or more of the command generation application 610, thememory 606, and/or another application or process executed by the pumpcontrol module 602 to obtain information or data characterizing currentuser interface status and verify that there is not an active alert oruser notification presented by a user interface element 608.

After verifying delivery is not suspended and that there are no activealerts, the monitoring application 612 obtains historical bolus datafrom memory 606, which includes information or data characterizing thetiming of boluses previously delivered by the infusion device 502 ormeals manually announced, entered or otherwise input to the infusiondevice 502 by the patient or another user. In some embodiments, mealsmay also be automatically detected by the pump control module 602 basedon sensed measurement values or other data. Based on the historicalbolus and meal data, the monitoring application 612 verifies that thepatient has not consumed a meal or administered a bolus within athreshold period of time (e.g., within the preceding 5 hours), andtherefore, is likely to be fasting.

In exemplary embodiments, the site monitoring process 800 also verifiesor otherwise confirms the physiological condition in the body of thepatient is substantially constant or steady before detecting oridentifying a fasting period for determining a fasting reference value(task 810). In this regard, the monitoring application 612 may verify orotherwise confirm that variations in the sensed measurement values overa preceding time interval are within a threshold range. For example, inone embodiment, the monitoring application 612 verifies that variationsin sensed glucose measurement values over the preceding two hours oftime is less than 20 milligrams per deciliter (mg/dL). Additionally, inexemplary embodiments, the monitoring application 612 also calculates orotherwise determines an estimated plasma insulin in the body of thepatient and verifies or otherwise confirms the plasma insulin rate ofchange is less than a threshold value. In this regard, the monitoringapplication 612 ensures any lingering active insulin in the body of thepatient is not unduly influencing sensed glucose measurement valuesduring the fasting period. As used herein, the estimated plasma insulinshould be understood as referring to an estimation of the concentrationof the total insulin present in a patient's blood (including both basaland bolus insulin delivered) and the estimated plasma insulin rate ofchange corresponds to the rate of change of the total insulinconcentration in the patient's blood. Here, it should also be noted thatin practical embodiments, the equations utilized to estimate plasmainsulin may vary depending on the type(s) of insulin being utilized toaccount for the rate or speed at which the insulin acts.

In one embodiment, the monitoring application 612 calculates orotherwise determines an estimated plasma insulin using the equation:

${{{Ip}(s)} = \frac{{Id}(s)}{\left( {{50s} + 1} \right)\left( {{70s} + 1} \right)}},$where s is the Laplace transform variable, Id(s) is the insulindelivered in units per hour (U/h), and Ip(s) is the estimated plasmainsulin in units per hour. In this regard, the estimated plasma insulinrate of change corresponds to the derivative of the estimated plasmainsulin equation. In one or more exemplary embodiments, the monitoringapplication 612 obtains historical delivery data from the commandgeneration application 610 and/or the memory 606 which indicates therespective timing and amounts of insulin delivered by the infusiondevice 102, 502 over a preceding period of time, and then calculates orotherwise determines the rate of insulin delivered (Id(s)) in units perhour at discrete instances over a preceding duration of time (e.g., thepreceding two hours) based on the historical delivery data. Using theinsulin delivered, the monitoring application 612 calculates orotherwise determines the estimated plasma insulin (Ip(s)) at discreteinstances over the preceding duration of time, and then determines theestimated plasma insulin rate of change between discrete estimatedplasma insulin values over the preceding duration of time, and verifiesthat the difference between the minimum and maximum estimated plasmainsulin rate of change values for that preceding duration is less than athreshold value. In this regard, a difference between minimum andmaximum estimated plasma insulin rate of change values that exceeds thethreshold value indicates that the sensed glucose measurement values aresusceptible to variations due to the plasma insulin in the body of theuser.

In one or more embodiments, the threshold value for the estimated plasmainsulin rate of change is calculated as a function of the patient'stotal daily insulin requirement. For example, in one embodiments, themonitoring application 612 verifies the deviation in the between theminimum and maximum estimated plasma insulin rate of change values overthe preceding two hours is less than a threshold value calculated usingthe following equation:

$\frac{TDI}{480},$where TDI is the patient's total daily insulin requirement. Thepatient's total daily insulin requirement may also be calculated ordetermined by the monitoring application 612 based on historical insulindelivery data, such as, for example, the mean or median amount ofinsulin delivered per 24-hour time window over a preceding interval(e.g., the median amount of insulin per 24 hours during the precedingweek). In other embodiments, the patient's total daily insulinrequirement could be input or otherwise provided by a user. In otherembodiments, the threshold value is calculated as a function of thepatient's basal infusion rate. For example, in one embodiment, themonitoring application 612 verifies the deviation in the between theminimum and maximum estimated plasma insulin rate of change values overthe preceding two hours is less than ten percent of the patient's basalrate. In yet other embodiments, the threshold value may be calculated asa function of another reference infusion rate for the patient (e.g., aminimum or maximum infusion rate limit associated with a particularoperating mode).

When variations in the measurement values for the physiologicalcondition in the body of the patient as well as variations in othermetric(s) characterizing the physiological condition in the body of thepatient are less than applicable thresholds or otherwise within anacceptable range, the site monitoring process 800 detects or otherwiseidentifies a fasting period suitable for determining a fasting value fora reference metric. Thereafter, whenever the patient consumes a meal,delivery is suspended, an alert is generated, or the patient's glucoselevel or metrics thereof become variable, the site monitoring process800 determines the current fasting period is over and reverts tomonitoring for another fasting period.

Still referring to FIG. 8, after detecting a fasting period, the sitemonitoring process 800 proceeds with obtaining sensed measurement valuescorresponding to the fasting period until the lifetime of the infusionset exceeds a threshold lifetime (tasks 812, 814). In this regard, theloop defined by tasks 802, 804, 806, 808, 810, 812, and 814 repeatsthroughout the initial portion of an infusion set's lifetime to obtainfasting sensed measurement values corresponding to the currentconfiguration of infusion set and insertion site that may be utilized todetermine a corresponding fasting reference value and subsequentlydetect a site loss condition once the lifetime of the infusion setextends beyond a certain duration. For example, in one embodiment, thefasting reference value(s) are determined based on sensed measurementvalues obtained during fasting periods within the first forty-eighthours after a new infusion set is initialized. In this regard, themonitoring application 612 may implement and initiate a timer upon a newinfusion set being initialized or utilized. In one or more embodiments,the monitoring application 612 stores or otherwise maintains sensedglucose measurement values obtained from the sensing arrangement 104,504 during fasting periods in memory 606 until the lifetime of theinsertion set exceeds a threshold duration.

After detecting a fasting period, when the site monitoring process 800determines the lifetime of the infusion set exceeds a thresholdlifetime, the site monitoring process 800 continues by monitoring for asite loss condition using the sensed measurement values obtained for thefasting period(s) during the initial portion of the infusion set'slifetime (task 816). In this regard, the monitoring application 612calculates or otherwise determines one or more fasting reference valuesbased on the obtained sensed measurement values corresponding to thefasting period(s) during the initial period of the infusion set'slifetime. As described in greater detail below in the context of thesite loss detection process 900 of FIG. 9, the monitoring application612 detects or otherwise identifies a site loss condition when anupdated reference value calculated based on obtained sensed measurementvalues during a current fasting period deviates from a fasting referencevalue by more than a threshold amount.

FIG. 9 depicts an exemplary site loss detection process 900 suitable forimplementation in conjunction with the site monitoring process 800 ofFIG. 8 to detect a site loss condition using a fasting reference valuedetermined based on sensed measurement values obtained during an initialphase of an infusion set's lifetime. The various tasks performed inconnection with the site loss detection process 900 may be performed byhardware, firmware, software executed by processing circuitry, or anycombination thereof. For illustrative purposes, the followingdescription refers to elements mentioned above in connection with FIGS.1-7. In practice, portions of the site loss detection process 900 may beperformed by different elements of an infusion system, however, forpurposes of explanation, the site loss detection process 900 may bedescribed herein primarily in the context of the infusion device 502,the pump control system 520, 600, and/or the pump control module 602. Itshould be appreciated that the site loss detection process 900 mayinclude any number of additional or alternative tasks, the tasks neednot be performed in the illustrated order and/or the tasks may beperformed concurrently, and/or the site loss detection process 900 maybe incorporated into a more comprehensive procedure or process havingadditional functionality not described in detail herein. Moreover, oneor more of the tasks shown and described in the context of FIG. 9 couldbe omitted from a practical embodiment of the site loss detectionprocess 900 as long as the intended overall functionality remainsintact.

In exemplary embodiments, the site loss detection process 900 isperformed once the lifetime of the current infusion set is greater thanan initialization period over which reference fasting sensed measurementvalues are obtained (e.g., task 816). For example, in one or moreembodiments, the site loss detection process 900 is performed once thelifetime of an infusion set is greater than forty-eight hours. The siteloss detection process 900 calculates or otherwise determines one ormore fasting reference measurement values based on sensed measurementvalues obtained during fasting periods within the initialization periodof the infusion set (task 902). For example, in one embodiment, themonitoring application 612 calculates an average fasting sensor glucoselevel for the patient by averaging the sensed glucose measurement valuesobtained from the sensing arrangement 104, 504 during the fastingperiod(s) (e.g., task 814) that occurred during the initial forty-eighthours of the infusion set's usage (e.g., task 812).

In another embodiment, the monitoring application 612 calculates anestimated amount of insulin needed to achieve a target blood glucoselevel from the patient's fasting blood glucose level. In practice, thetarget blood glucose level may be a limit associated with an autonomousoperating mode supported by the infusion device 102, 502, and in someembodiments, may be patient-specific. For example, in one embodiment,the target blood glucose level may be an upper glucose limit associatedwith a closed-loop operating mode. In another embodiment, the targetblood glucose level may be the same target or reference glucose valueassociated with the closed-loop operating mode. The estimated amount ofinsulin needed to achieve a target blood glucose level may be calculatedusing the equation:

${{{Ip}(t)} + \frac{{FBG}_{T} - {FBG}}{{- 5400}/{TDI}}},$where FBG is the fasting sensor glucose level, FBG_(T) is the targetblood glucose level, TDI is the patient's total daily insulinrequirement, and Ip(t) is the estimated plasma insulin as describedabove. Thus, in one embodiment, to determine a reference estimatedamount of insulin during fasting periods, the monitoring application 612calculates or otherwise determines estimated plasma insulin values forthe fasting period(s) during the initialization period and calculatesthe reference estimated amount of insulin as a function of the averageestimated fasting plasma insulin values during the initialization periodand the average fasting sensor glucose level during the initializationperiod. In some embodiments, the reference estimated amount of insulinat fasting may be calculated or otherwise determined substantially inreal-time during the initialization period and dynamically updated on arolling basis to obtain a moving average over the initialization periodhaving a final value that corresponds to the fasting reference value.

After determining a fasting reference value, the site loss detectionprocess 900 continues by identifying or otherwise determining when afasting period exists, and in response to detecting a fasting period,obtains a current sensed measurement value, calculates or otherwisedetermines an updated (or current) value for the reference metric basedon the current sensed measurement value, and then detects or identifiesa site loss condition based on the difference between the updatedreference metric value and the fasting reference value (tasks 904, 906,908, 910). In a similar manner as described above in the context of FIG.8, the monitoring application 612 identifies a fasting period whendelivery is not suspended (e.g., task 802), there are no active alertsor notifications (e.g., task 804), there are no meals or boluses withina preceding period of time (e.g., tasks 806, 808), and the patient'sglucose level is stable (e.g., task 810). When a fasting period exists,the monitoring application 612 obtains the current or most recent sensedglucose measurement value from the sensing arrangement 104, 504, andthen calculates a current value for the reference metric substantiallyin real-time using the current sensed glucose measurement value. In thisregard, when the reference metric is an estimated amount of insulinneeded to achieve a target blood glucose level, the monitoringapplication 612 calculates or otherwise determines a current estimatedamount of insulin needed to achieve the target blood glucose level fromthe current glucose level as a function of the current sensed glucosemeasurement value and the current estimated plasma insulin level usingthe equations described above.

In exemplary embodiments, the monitoring application 612 detects orotherwise identifies a site loss condition when the difference betweenthe fasting reference value and the current or updated value for thereference metric deviates from the fasting reference value by more thana threshold percentage. For example, in one embodiment, the monitoringapplication 612 detects a site loss condition when the updated referencemetric value is more than thirty percent greater than the fastingreference value. In such embodiments, if the current estimated amount ofinsulin needed to achieve the target blood glucose level is greater thanthe fasting reference estimated amount of insulin by more than thirtypercent, a site loss condition is detected. Similarly, in embodimentswhere the glucose level is utilized as the reference metric, a site losscondition may be detected if the current sensed glucose measurementvalue is greater than the average of the sensed glucose measurementvalues from the fasting period(s) during the initialization period bymore than thirty percent.

Still referring to FIG. 9, in response to detecting a site losscondition, the site loss detection process 900 generates or otherwiseprovides a user notification or alert that indicates a site losscondition (task 912). In exemplary embodiments, the monitoringapplication 612 generates or otherwise provides a notification, via theuser interface 608, that indicates that the patient needs to change theinfusion set, inspect the infusion set (or insertion thereof) forpotential malfunction, change the insertion site, and/or the like. Inthis regard, in some embodiments, the monitoring application 612 mayanalyze historic delivery data, measurement data, historical insertionsite location information, and/or other historical information toprovide guidance as to the cause of the notification. For example, basedon the current lifetime of the current infusion set relative topreceding infusion sets, the frequency or rate at which the currentinsertion site is utilized by the patient, and potentially other metricsthat may be calculated using historic data, the monitoring application612 may be able to determine or otherwise assign a likelihood orprobability to the potential causes of the site loss notification andprovide corresponding guidance to the patient (e.g., by listingreplacing the infusion set, inspecting the infusion set, changing theinsertion site, and the like in order of likelihood).

In one or more exemplary embodiments, the site loss detection process900 is persistently performed once the lifetime of an infusion setexceeds a threshold amount. In this regard, while an initial insertionsite loss notification may be cleared by a patient after inspecting theinsertion site, the site loss detection process 900 may generateadditional site loss notifications during subsequent fasting periods toprovide continual reminders to the patient throughout the lifetime ofthe infusion set. Thus, if the patient chooses not to replace theinfusion set initially, the patient may be subsequently apprised of thefact that the action taken in response to a preceding notification wasnot effective at resolving the discrepancy between the current referencemetric values and the fasting reference value from the initializationperiod. Accordingly, the likelihood of the patient utilizing theinfusion set for a prolonged duration or other potential adverse eventsis reduced.

By virtue of the subject matter described herein, a more flexiblereplacement schedule for infusion sets (and corresponding insertion siterotation) may be adopted, thereby allowing infusion sets to be used fora longer duration rather than replace preemptively. At the same time,infusion sets requiring relatively early replacement may also be alertedwhen a site loss condition is detected rather than waiting for a fixedtime period to elapse after insertion. Site loss notifications may alsoreduce or eliminate the need for patients to monitor or track thelifetime of the current infusion set, thereby reducing the burden onpatients and improving the user experience without compromising patientoutcomes.

For the sake of brevity, conventional techniques related to glucosesensing and/or monitoring, closed-loop glucose control, sensorcalibration, electrical signals and related processing, user interfaces,alerting, and other functional aspects of the subject matter may not bedescribed in detail herein. In addition, certain terminology may also beused in the herein for the purpose of reference only, and thus is notintended to be limiting. For example, terms such as “first”, “second”,and other such numerical terms referring to structures do not imply asequence or order unless clearly indicated by the context. The foregoingdescription may also refer to elements or nodes or features being“connected” or “coupled” together. As used herein, unless expresslystated otherwise, “coupled” means that one element/node/feature isdirectly or indirectly joined to (or directly or indirectly communicateswith) another element/node/feature, and not necessarily mechanically.

While at least one exemplary embodiment has been presented in theforegoing detailed description, it should be appreciated that a vastnumber of variations exist. It should also be appreciated that theexemplary embodiment or embodiments described herein are not intended tolimit the scope, applicability, or configuration of the claimed subjectmatter in any way. For example, the subject matter described herein isnot necessarily limited to the infusion devices and related systemsdescribed herein. Moreover, the foregoing detailed description willprovide those skilled in the art with a convenient road map forimplementing the described embodiment or embodiments. It should beunderstood that various changes can be made in the function andarrangement of elements without departing from the scope defined by theclaims, which includes known equivalents and foreseeable equivalents atthe time of filing this patent application. Accordingly, details of theexemplary embodiments or other limitations described above should not beread into the claims absent a clear intention to the contrary.

What is claimed is:
 1. A method of operating an infusion device operableto deliver insulin to a body of a patient, the method comprising:obtaining, from a sensing arrangement, sensed glucose measurement valuesof a glucose level in the body of the patient during fasting periodsduring an initial period after initialization of an infusion setassociated with the infusion device; determining a fasting amount ofinsulin in the body of the patient during the fasting periods;determining a reference insulin estimate for achieving a referenceglucose value based at least in part on the fasting amount of insulinand the sensed glucose measurement values; and after the initial period:obtaining, from the sensing arrangement, an updated glucose measurementvalue during a subsequent fasting period; determining a current amountof insulin in the body of the patient; determining a current insulinestimate for achieving the reference glucose value based at least inpart on the current amount of insulin and the updated glucosemeasurement value; and generating an insertion site notification basedon a relationship between the current insulin estimate and the referenceinsulin estimate.
 2. The method of claim 1, further comprisingdetermining the current amount of insulin based on historical deliverydata corresponding to preceding operation of the infusion device todeliver the insulin to the body of the patient.
 3. The method of claim2, further comprising determining a total daily insulin value based onthe historical delivery data, wherein determining the current insulinestimate comprises calculating the current insulin estimate based on theupdated glucose measurement value, the reference glucose value, thecurrent amount of insulin, and the total daily insulin value.
 4. Themethod of claim 2, further comprising verifying the glucose level in thebody of the patient is stable prior to obtaining the sensed glucosemeasurement values.
 5. The method of claim 2, further comprisingverifying normal operation of the infusion device prior to obtaining thesensed glucose measurement values.
 6. The method of claim 2, furthercomprising verifying absence of a meal within a threshold time periodprior to obtaining the sensed glucose measurement values.
 7. The methodof claim 6, further comprising verifying the glucose level in the bodyof the patient is stable prior to obtaining the sensed glucosemeasurement values.
 8. The method of claim 1, further comprisingverifying absence of a meal within the threshold time period prior toobtaining the updated glucose measurement value.